BX-100 Nyström - Hanstorp Functional Cytology: detection of cellular damage
Project Summary: Objectives, expected results, summary of the Project plan
This research project is aimed at (i) achieving an understanding of the molecular mechanisms underlying cellular deterioration and rejuvenation and (ii) investigate whether oxidative damage to target proteins are causative agents of age-related senescence and diseases. We will embark on an interdisciplinary collaboration between biologists and physicists to develop tools for single cell analysis that will allow high-throughput screenings of cellular damages associated with aging and disease. By employing molecular vibration microscopy, i.e. Coherent Antistokes Raman Spectroscopy (CARS), we will make possible in situ imaging of disease-related damages in single cells. We aim to develop CARS with high spatial resolution and sensitivity in order to directly detect oxidized proteins by their special vibration profiles in intact living cells without staining or introducing reporters. The CARS setup will be combined with multi-photon imaging and optical manipulation technologies, enabling simultaneous visualization of fluorescence and vibration signals and optical surgery at the single cell level. These latter approaches will be instrumental in developing “Imaging Genetics”, i.e. high-throughput screenings based on novel cytological read-outs of choice and the subsequent isolation, using tweezers, of single mutant cells within large random and ordered mutant libraries. Our facility is one of only a few CARS laboratories in the world, and the only one focusing on proteins and their oxidative modification. It will also be the only one operating with a laser tweezers/manipulation platform. This, together with Nyströms recent results on an in situ approach to study oxidative carbonylation of proteins in single cells gives us a unique competitive edge.
Keywords for the project (to be found in international databases)
Cellular deterioration, Replicative Aging, Oxidative Damage, Imaging Genetics, Optical Tweezers, Laser Scalpels, Lab-on-a-chip, CARS, Multiphoton Microscopy.